Tissue engineering is one of new fields emerged with the development of science. It is a multidisciplinary science integrating basic concept such as life science, engineering and medicine with scientific technologies for understanding correlation between structure and functions of biological tissues, and further an applied science objected to maintain, enhance or recover functions of the body by making artificial tissues, which can be transplanted to the body for replacing or regenerating damaged tissues or organs to normal tissue.
A representative tissue engineering technique applies a technique comprising the following procedures. First of all, a required tissue is collected form a patient body, cells are isolated form the tissue sample, the isolated cells are proliferated as needed by culture, the proliferated cells are seeded to a porous biodegradable polymer support body and cultured in vitro for a certain period of time to obtain a hybrid type cell/polymer structure, and then the structure is transplanted to the human body again. In the case of most tissues or organs, the cells after transplantation are supplied with oxygen and nutrients by body fluid diffusion until new blood vessels are formed, and then when blood is supplied through blood vessels grown in the human body, cells are proliferated and differentiated so as to form new tissues and organs, while the polymer support body is removed by degradation.
Thus, for this tissue engineering study, first of all, it is important to manufacture a biodegradable polymer support body, which is similar with a living tissue. Main requirements of support body materials used for regenerating human tissues are that: it should play a role as a substrate or a frame so as to make tissue cells adhere to the material surface and to form a tissue having a three dimensional structure, and it should also play a role as a middle barrier located between the transplanted cells and host cells. This means that it should have non-toxic biocompatibility not causing blood clotting or inflammatory reaction after transplantation.
When a joint is damaged, the damaged joint is difficult to be autochthonously regenerated because there is no blood vessels, nerves and lymphatic tissues in the articular cartilage. Accordingly, in the articular cartilage, small damage may cause development of wound and degeneration of the joint. Thus, in order to recover and maintain functions of bone and cartilage tissues, many medical methods are being attempted.
A cartilage is a tissue embryologically derived from the mesoderm like as a bone tissue, and forms an endoskeleton together with a bone. Further, when the cartilage is severely damaged, a bone tissue below the cartilage as well as the cartilage may be damaged. Like this, the cartilage and the bone are intimately working tissues, but the previous tissue engineering therapy of the bone and the cartilage treated them separately.
Specifically, as previous operation methods for clinically regenerating cartilages, method for regenerating only cartilages, for example: (1) a method of inducing differentiation of stem cells into cartilage cells, (2) a method of transplanting bone tissues, cartilage tissues, self or homogeneous cartilage tissues to the cartilage defected region, (3) a method of transplanting tissues (perichondrium or periosteum) or compounds, which can induce cartilages, on the surface, of the cartilage defected region, and (4) a method of inducing cartilage regeneration by transplanting cartilage cells to the cartilage defected region by cartilage cell implantation are used.
However, as mentioned above, the bone and the cartilage are intimately working tissues. Accordingly, in the case of the previous method treating the cartilage and the bone separately, there were problems of weak cohesiveness and long recovering time.
In order to solve the problems, support bodies, which can treat the bone and the cartilage at the same time, are being developed.
For tissue engineering articular cartilage regeneration, C. Hassper et al manufactured an osteochondral construct by modeling an articular surface through CT image and by machining the surface identically with a real articular surface. (Carl Haasper, et. al, “A system for engineering an osteochondral construct in the shape of an articular surface: Preliminary results,” Annals of Anatomy, Vol. 190, pp. 351˜359 2008). They manufactured the construct as a dual structure by compressing collagen-1, where cells are planted on one side thereof, by using a commercialized Tutobone (heterogeneous bone graft). However, there were problems that the materials are very expensive, and it is impossible to control the internal structure of a carrier. Further, in the recent studies, a complex support body manufactured by culturing each cell on a poly(glycolic acid) (PGA) support body and a poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) support body of the bone part, separately followed by linking the two support bodies by using a suture (Schaefer et al., Biomaterials, 2000, 21, 2599-2606), a collagen/PLGA sponge support body (Guoping Chen et al., Materials Science and engineering C 26 (2006) 118. 123), and the like had been tried. However, development of a complex support body for bones and cartilages having excellent effect are still needed.
Further, many researchers are trying various methods for making a polymer to a porous structure, for example, a salt leaching method, which is mixing single crystal salt, drying and then leaching the salt by dissolving in water (Solvent-casting and particulate-leaching technique: A. G. Mikos et al, Polymer, 35, 1068, 1994), a method of swelling a polymer by using CO2, gas (Gas foaming technique: L. D. Harris et al, J. Biomed. Mater. Res., 42, 396, 1998), a method for making a polymer fiber to a non-woven fabric in the form of a polymer mesh (Fiber extrusion and fabric forming process: K. T. Paige et al, Tissue Engineering, 1, 97, 1995), a phase separation method making pores by soaking the solvent contained in a polymer solution in a non-solvent (Thermally induced phase separation technique: C. Schugens et al, J. Biomed. Mater. Res., 30, 449, 1996), an emulsion freeze-drying method, which is manufacturing an emulsion solution by mixing a polymer solution and water, and then freezing with liquid nitrogen so as to freeze-dry (Emulsion freeze-drying method: K. Whang et al, Polymer, 36, 837, 1995).
However, the above methods had problems that it is generally difficult to control the pore size of a support body, the surface and porosity of the obtained polymer support body, and it is difficult to form open structure between pores.